Fast-Refeeding-Induced Hyperphagia Requires Ghrelin Signaling

FERNÁNDEZ G; CABRAL A; DE FRANCESCO P N; GARCÍA ROMERO G; PORTIANSKY E L; REYNALDO M; PERELLÓ M

Mar del Plata

Congreso; XXX Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Sociedad Argentina de Investigación en Neurociencias

Animals refed after fasting display a robust hyperphagia, which aims at restoring the energy balance. Interestingly, hyperphagia persists even after animals have reached their energy needs if fasting is severe. The mechanism regulating the magnitude of the compensatory events of hyperphagia are currently unclear. Here, we tested the long-term eating behavior of mice exposed to a fast-refeed paradigm and also analyzed the dynamic of the ghrelin system -the only known hormone able to increase food intake- under these circumstances. In addition, we tested the eating behavior after fast-refeeding in mice lacking the ghrelin receptor. We found that previously fasted wild-type mice display a significant increase of the total food intake that continues for 4 days after refeeding. Fasting increases both ghrelin plasma levels and the ghrelin binding in some, but not all, hypothalamic nuclei. This binding was particularly increased at the GABAergic terminals within the hypothalamic arcuate nucleus. Notably, ghrelin binding and sensitivity to exogenous ghrelin administration remained increased even after 4 days of refeeding. In contrast, ghrelin receptor deficient mice exposed to a fast-refeed paradigm failed to increase the total food intake after refeeding. We conclude that ghrelin signaling in GABAergic terminals increases under fasting and that this readjustment of the ghrelin system is involved in the fast-refeeding-induced hyperphagia. Supported by PICT2011-2142 and PICTO2013-0065